The mammalian Target of Rapamycin Complex 1 (mTORC1)-signaling system plays a critical role in the maintenance of cellular homeostasis by sensing and integrating multiple extracellular and intracellular cues. Therefore, uncovering the effectors of mTORC1 signaling is pivotal to understanding its pathophysiological effects. Here we report that the transcription factor forkhead/winged helix family k1 (Foxk1) is a mediator of mTORC1-regulated gene expression. Surprisingly, Foxk1 phosphorylation is increased upon mTORC1 suppression, which elicits a 14-3-3 interaction, a reduction of DNA binding, and nuclear exclusion. Mechanistically, this occurs by mTORC1-dependent suppression of nuclear signaling by the Foxk1 kinase, Gsk3. This pathway then regulates the expression of multiple genes associated with glycolysis and downstream anabolic pathways directly modulated by Foxk1 and/or by Foxk1-regulated expression of Hif-1α. Thus, Foxk1 mediates mTORC1-driven metabolic rewiring, and it is likely to be critical for metabolic diseases where improper mTORC1 signaling plays an important role.
Pubmed ID: 29861159 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
This monoclonal targets Vinculin antibody produced in mouse
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets GSK-3alpha/beta
View all literature mentionsThis polyclonal targets Phospho-GSK-3alpha/beta (Ser21/9)
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis unknown targets
View all literature mentionsThis polyclonal targets LMNA
View all literature mentionsThis monoclonal targets GAPDH antibody produced in mouse
View all literature mentionsThis monoclonal targets Phospho-S6 Ribosomal Protein (Ser240/244) (D68F8) XP Rabbit mAb
View all literature mentionsThis monoclonal targets S6 Ribosomal Protein (54D2) Mouse mAb
View all literature mentionsThis polyclonal targets HIF-1α
View all literature mentionsThis polyclonal targets FOXK1 - ChIP Grade
View all literature mentionsCell line RT-4 is a Cancer cell line with a species of origin Homo sapiens (Human)
View all literature mentions